Process for preparing alkyl pyroglutamic acids

ABSTRACT

Disclosed are compounds of formulae: 
     
       
         
         
             
             
         
       
     
     and salts, hydrates, or solvates thereof, where R 1 , R 2 , R 3 , R 5 , and R 6  are defined herein, compositions containing these compounds, methods of preparing these compounds, and methods of using these compounds in a variety of applications, such as a surfactant or additive in personal care products.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims benefit of U.S. Provisional Application Ser. No.61/576,023, filed Dec. 15, 2011, the disclosure of which is incorporatedherein by reference in its entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This disclosure relates to compounds and compositions suitable for usein surfactants. In particular, the disclosure relates to alkylpyroglutamic acid compounds.

2. Description of Related Art

The large shift towards environmentally friendly surfactants hasresulted in the need for the industry to provide readily biodegradableand non-toxic surfactants and additives. Surfactants and additives withrenewable content can be preferable to their synthetic counterparts withdemand being driven by life sustainability initiatives, preferred buyingprograms and consumer trends.

Alcohol ethoxy sulfates (AES) is a class of anionic surfactant commonlyused in personal care shampoo formulation. The trace byproduct from themanufacturing processes of AES (alkoxylation and sulfation), and theskin irritancy associated with AES are not desirable in personal careapplications. An ethylene oxide-free (EO-free) and sulfate-freesurfactant that is non-irritating is much more preferable in personalcare.

Common EO-free and sulfate-free surfactant personal care surfactants arefatty acid soaps, betaines, alpha olefin sulfonates, sulfosuccinates,esters, alkyl polyglucosides, fatty acyl amino acids, fatty amineoxides, and quaternaries. Two common commercially available amino acidsurfactants are acyl glutamate and acyl sarcosinate. Acyl glutamate isderived from natural fatty acids and natural glutamic acid, while acylsarcosinate is derived from natural fatty acids and synthetic glycine.In either case, these amino acid surfactants are commonly accepted asnon-toxic and mild. They are used mainly in personal care applications,but not as widely used as alkyl polyglucosides (APG) due, at least inpart, to the use of fatty acid chlorides as intermediates in amideformation with the amino acid of choice.

The preparation and use of corrosive acid chlorides imparts cost to theamide-based amino acid surfactants and generation of a full equivalentof waste from the chlorinating reagent. Additionally, the isolation ofthe desired fatty acid amide from salt byproduct and water also addscost relative to other surfactants.

SUMMARY OF THE INVENTION

In a broad aspect, the disclosure provides compounds or mixturesthereof, and formulations containing said compounds that areN-alkylpyroglutamic acids, which may be derived from glutamic acid andaldehydes. The properties and composition of the N-alkylpyroglutamicacid derivatives are very dependent on the features of the aldehyde, andthe method of production which controls the composition of theseglutamic acid derivatives.

Thus, one aspect of the disclosure (embodiment 1) provides compounds offormula (I):

or acceptable salts, hydrates, or solvates thereof; wherein

-   R₁ is hydrogen, C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, M⁺, or a    polyoxyalkylene moiety having oxyalkyl groups that are the same or    different, and where the polyoxyalkylene moiety is capped or    uncapped;

where M⁺ is a cation forming a salt;

-   R₂ and R₃ are independently C₂-C₂₄ alkyl, C₂-C₂₄ alkenyl, or C₂-C₂₄    alkynyl, each optionally substituted with one or more of R₄; and    wherein R₄ is halogen, —CN, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆    alkynyl, C₁-C₆ haloalkyl, —NH(C₁-C₆ alkyl), —N(C₁-C₆ alkyl)₂, —OH,    C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆ alkyl), —CON(C₁-C₆    alkyl), —CON(C₁-C₆ alkyl)₂, C₃-C₈ cycoalkyl, aryl, heteroaryl, or    heterocyclyl, wherein each cycloalkyl, aryl, heteroaryl, and    heterocyclyl are optionally substituted with one or more of halogen,    —CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆ alkyl), —N(C₁-C₆    alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆    alkyl), —CON(C₁-C₆ alkyl), or —CON(C₁-C₆ alkyl)₂;    -   or R₄ is polyoxyalkylene moiety having oxyalkyl groups that are        the same or different, and where the polyoxyalkylene moiety is        capped or uncapped.

The disclosure also provides compositions comprising a compound offormula (I) or mixtures thereof, and at least one additive, excipient ordiluent.

Another aspect of the disclosure (embodiment 2) provides compositionscomprising at least two compounds selected from the compounds of formula(II):

or acceptable salts, hydrates, or solvates thereof; wherein

-   -   R₅ is hydrogen, C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, M⁺, or a        polyoxyalkylene moiety having oxyalkyl groups that are the same        or different, and where the polyoxyalkylene moiety is capped or        uncapped;        -   where M⁺ is a cation forming a salt;    -   R₆ is unbranched or branched C₂-C₂₄ alkyl, unbranched or        branched C₂-C₂₄ alkenyl, unbranched or branched C₂-C₂₄ alkynyl,        C₃-C₈ cycloalkyl, or C₃-C₈ cycloalkyl(C₁-C₆ alkyl), each        optionally substituted with one or more of R₇; and    -   wherein R₇ is halogen, —CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂,        —NH(C₁-C₆ alkyl), —N(C₁-C₆ alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆        haloalkoxy, —CO₂H, —CO₂(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl),        —CON(C₁-C₆ alkyl)₂, C₃-C₈ cycloalkyl, aryl, heteroaryl, or        heterocyclyl, wherein each cycloalkyl, aryl, heteroaryl, and        heterocyclyl are optionally substituted with one or more of        halogen, —CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆        alkyl), —N(C₁-C₆ alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy,        —CO₂H, —CO₂(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl), or —CON(C₁-C₆        alkyl)₂; and        of formula (III):

or acceptable salts, hydrates, or solvates thereof; wherein

-   -   each R₈ is independently hydrogen, C₁-C₆ alkyl, C₁-C₆        hydroxyalkyl, M⁺, or a polyoxyalkylene moiety having oxyalkyl        groups that are the same or different, and where the        polyoxyalkylene moiety is capped or uncapped;    -   where M⁺ is a cation forming a salt;    -   R₉ is unbranched or branched C₂-C₂₄ alkyl, unbranched or        branched C₂-C₂₄ alkenyl, unbranched or branched C₂-C₂₄ alkynyl,        C₃-C₈ cycloalkyl, or C₃-C₈ cycloalkyl(C₁-C₆ alkyl), each        optionally substituted with one or more of R₁₀; and wherein R₁₀        is halogen, —CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆        alkyl), —N(C₁-C₆ alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy,        —CO₂H, —CO₂(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl)₂,        C₃-C₈ cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein        each cycloalkyl, aryl, heteroaryl, and heterocyclyl are        optionally substituted with one or more of halogen, —CN, C₁-C₆        alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆ alkyl), —N(C₁-C₆        alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆        alkyl), —CON(C₁-C₆ alkyl), or —CON(C₁-C₆ alkyl)₂.

The disclosure also provides methods of preparing compounds of thedisclosure and the intermediates used in those methods. In particular,the disclosure provides a method for preparing a compound of formula(IV) or a mixture of one or more compounds of formula (IV), (embodiment3):

or acceptable salts, hydrates, or solvates thereof; wherein

-   -   R₁₁ is hydrogen, C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, M⁺, or a        polyoxyalkylene moiety having oxyalkyl groups that are the same        or different, and can be capped or uncapped; where M⁺ is a        cation forming a salt;    -   R₁₂ is unbranched or branched C₃-C₂₄ alkyl, unbranched or        branched C₃-C₂₄ alkenyl, or unbranched or branched C₃-C₂₄        alkynyl, each optionally substituted with one or more of R₁₅;        and    -   wherein R₁₅ is halogen, —CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂,        —NH(C₁-C₆ alkyl), —N(C₁-C₆ alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆        haloalkoxy, —CO₂H, —CO₂(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl),        —CON(C₁-C₆ alkyl)₂, C₃-C₈ cycloalkyl, aryl, heteroaryl, or        heterocyclyl, wherein each cycloalkyl, aryl, heteroaryl, and        heterocyclyl are optionally substituted with one or more of        halogen, —CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆        alkyl), —N(C₁-C₆ alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy,        —CO₂H, —CO₂(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl), or —CON(C₁-C₆        alkyl)₂;        comprising        treating a glutamate of formula:

-   -   wherein each R₁₄ is independently selected form hydrogen, M⁺,        C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, —(C₁-C₆ alkyl-0)₁₋₄H, aryl,        aryl(C₁-C₆ alkyl), or polyoxyalkylene unit;        with an aldehyde of formula:

-   -   wherein R₁₃ is C₁-C₂₃ alkyl, C₂-C₂₃ alkenyl, or C₂-C₂₃ alkynyl,        each optionally substituted with one or more of R₁₅.

The disclosure also provides intermediates that are useful in making thecompounds of formula (I)-(IV).

The disclosure further provides uses of the compounds and compositionsof the disclosure as a surfactant, or surface active additive. Thesecompounds and compositions that are used as surfactants demonstratepotential for enhanced performance in personal care formulationapplications (e.g., to provide good foam and low skin irritation forshampoo and body wash formulations). Thus, the disclosure also providesa method of using the compounds and the compositions of the disclosurein personal care formulations.

DETAILED DESCRIPTION OF THE INVENTION

In embodiment 4, the disclosure provides compounds of embodiment 1wherein R₁ is hydrogen or M⁺ (where M⁺ is a cation forming a salt, suchas any base addition salt). In embodiment 5, the disclosure providescompound of embodiment 4, wherein R₁ is hydrogen. In embodiment 6, thedisclosure provides compound of embodiment 4, wherein R₁ is M⁺.Embodiment 7 provides compounds of embodiment 6, wherein R₁ is Na⁺, orK⁺.

In embodiment 8, the disclosure provides compounds of embodiment 1wherein R₁ is a polyoxyalkylene moiety having oxyalkyl groups that arethe same or different, and where the polyoxyalkylene moiety is capped oruncapped. In embodiment 9, the polyoxyalkylene moiety is polyethyleneglycol, methoxypolyethylene glycol, polypropylene glycol,polytetramethylene glycol, or a combination thereof. In embodiment 10,the polyoxyalkylene moiety is polyethylene glycol, methoxypolyethyleneglycol, polypropylene glycol, or a combination thereof. Embodiment 11provides compounds according to any preceding embodiment where thepolyoxyalkylene moiety is polyethylene glycol or methoxypolyethyleneglycol.

In embodiment 12, the disclosure provides compounds of any one ofembodiments 8-11 wherein polyoxyalkylene moiety (e.g., polyethyleneglycol or methoxypolyethylene glycol) has a molecular weight betweenabout 80 and about 5000. In embodiment 13, the molecular weight isbetween about 200 and about 3500. In embodiment 14, the molecular weightis between about 200 and about 1000.

In embodiment 15, the disclosure provides compounds of any one ofembodiments 1 or 4-14 wherein R₂ is C_(n) alkyl, and R₃ is C_(n-2)alkyl, each optionally substituted with one or more of R₄, and wherein nis 4-12. In embodiment 16, the disclosure provides compound ofembodiment 15, wherein n is 8-12. In embodiment 17, n is 10. Inembodiment 18, the disclosure provides compound of embodiment 15,wherein n is 4-7. In embodiment 19, n is 5.

Embodiment 20 provides compounds according to any one of embodiments15-19, wherein R₄ is halogen, —ON, C₁-C₆ alkyl, C₁-C₆ haloalkyl,—NH(C₁-C₆ alkyl), —N(C₁-C₆ alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy,—CO₂H, —CO₂(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl), or —CON(C₁-C₆ alkyl)₂. Inembodiment 21, the disclosure provides compound of embodiment 20,wherein R₄ is C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH(C₁-C₆ alkyl), —N(C₁-C₆alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, or —CO₂(C₁-C₆ alkyl).

Embodiment 22 provides compounds according to any one of embodiments15-19, wherein R₄ is C₁-C₆ alkyl, —OH, C₁-C₆ alkoxy, —CO₂(C₁-C₆ alkyl),or —CON(C₁-C₆ alkyl). Embodiment 23 provides compounds according to anyone of embodiments 15-19, where R₄ is aryl, or heteroaryl.

Embodiment 24 provides compounds according to any one of embodiments15-19, where both R₂ and R₃ are unsubstituted.

Embodiment 25 provides compounds of embodiment 1 which are:

In embodiment 26, the disclosure provides composition of embodiment 2further comprising at least one additive, excipient or diluent.Embodiment 27 provides compositions of embodiment 2 or 26, wherein eachcompound is present in about 0.01 to about 100 weight %. In embodiment28, the composition of embodiment 27 is where at least one compound ispresent in about >10 weight %. In embodiment 29, the composition ofembodiment 28 is where at least one compound is present in about >50weight %.

In embodiment 30, the disclosure provides composition of any one ofembodiments 2 or 26-29 where R₅ is hydrogen or M⁺ (where M⁺ is a cationforming a salt, such as any base addition salt). In embodiment 31, thedisclosure provides composition of embodiment 30, wherein R₅ ishydrogen. In embodiment 32, the disclosure provides composition ofembodiment 30, wherein R₅ is M⁺. Embodiment 33 provides composition ofembodiment 32, wherein R₅ is Na⁺, or K⁺.

In embodiment 34, the disclosure provides composition of any one ofembodiments 2 or 26-29 wherein R₅ is a polyoxyalkylene moiety havingoxyalkyl groups that are the same or different, and where thepolyoxyalkylene moiety is capped or uncapped. In embodiment 35, thepolyoxyalkylene moiety is polyethylene glycol, methoxypolyethyleneglycol, polypropylene glycol, polytetramethylene glycol, or acombination thereof. In embodiment 36, the polyoxyalkylene moiety ispolyethylene glycol, methoxypolyethylene glycol, polypropylene glycol,or a combination thereof. Embodiment 37 provides composition accordingto any preceding embodiment where the polyoxyalkylene moiety ispolyethylene glycol or methoxypolyethylene glycol.

In embodiment 38, the disclosure provides compositions of any one ofembodiments 34-37 wherein polyoxyalkylene moiety (e.g., polyethyleneglycol or methoxypolyethylene glycol) has a molecular weight betweenabout 80 and about 5000. In embodiment 39, the molecular weight isbetween about 200 and about 3500. In embodiment 40, the molecular weightis between about 200 and about 1000.

In embodiment 41, the disclosure provides composition of any one ofembodiments 2 or 26-40 where R₆ is unbranched or branched C₂-C₂₄ alkyl,or unbranched or branched C₂-C₂₄ alkenyl, each optionally substitutedwith one or more of R₇. In embodiment 42, R₆ is unbranched or branchedC₂-C₂₄ alkyl, optionally substituted with one or more of R₇.

In embodiment 43, the disclosure provides composition of any one ofembodiments 2 or 26-42 where each R₈ independently is hydrogen or M⁺(where M⁺ is a cation forming a salt, such as any base addition salt).In embodiment 44, the disclosure provides composition of embodiment 43,wherein each R₈ is hydrogen. In embodiment 45, the disclosure providescomposition of embodiment 43, wherein each R₈ is M⁺. Embodiment 46provides composition of embodiment 45, wherein each R₈ is Na⁺, or K⁺.

In embodiment 47, the disclosure provides composition of any one ofembodiments 2 or 26-42 wherein at least one R₈ is a polyoxyalkylenemoiety having oxyalkyl groups that are the same or different, and wherethe polyoxyalkylene moiety is capped or uncapped. In embodiment 48, thepolyoxyalkylene moiety is polyethylene glycol, methoxypolyethyleneglycol, polypropylene glycol, polytetramethylene glycol, or acombination thereof. In embodiment 49, the polyoxyalkylene moiety ispolyethylene glycol, methoxypolyethylene glycol, polypropylene glycol,or a combination thereof. Embodiment 50 provides composition accordingto any preceding embodiment where the polyoxyalkylene moiety ispolyethylene glycol or methoxypolyethylene glycol.

In embodiment 51, the disclosure provides compositions of any one ofembodiments 49-50 wherein polyoxyalkylene moiety (e.g., polyethyleneglycol or methoxypolyethylene glycol) has a molecular weight betweenabout 80 and about 5000. In embodiment 52, the molecular weight isbetween about 200 and about 3500. In embodiment 53, the molecular weightis between about 200 and about 1000.

In embodiment 54, the disclosure provides composition of any one ofembodiments 2 or 26-53 where R₉ is unbranched or branched C₂-C₂₄ alkyl,or unbranched or branched C₂-C₂₄ alkenyl, each optionally substitutedwith one or more of R₁₀. In embodiment 55, R₉ is unbranched or branchedC₂-C₂₄ alkyl, optionally substituted with one or more of R₁₀.

Embodiment 56 provides compositions according to embodiment 2 or 26comprising at least two compounds of formula (II). In embodiment 57, thecomposition of embodiment 56 comprises at least two compounds that are:

Embodiment 58 provides compositions according to embodiment 56 or 57further comprising additional compounds according to formula (II) or(III).

Depending on the method of production, unique composition of compound offormula (II) and a compound of formula (III) can be produced. Thus,embodiment 59 provides compositions according to embodiment 2 or 26comprising at least one compound of formula (II) and one compound offormula (III). In embodiment 60, the composition of embodiment 59comprises at least two compounds that are:

Embodiment 61 provides compositions according to embodiment 59 or 60further comprising additional compounds according to formula (II) or(III).

The disclosure also provides a compound according to any one ofembodiments 1 or 4-25 or a composition according to any one ofembodiment 2 or 26-61 for use as a surfactant, or surface activeadditive. (Embodiment 62)

The disclosure also provides a compound according to any one ofembodiments 1 or 4-25 or a composition according to any one ofembodiment 2 or 26-61 for use in personal care (shampoo and body wash)formulations, oil recovery, agricultural adjuvants, pesticide inerts,pharmaceutical inerts, textile processing, emulsion polymerization,polymer processing, paint additives, household and institutionalcleaning. (Embodiment 63)

In embodiment 64, the disclosure provides methods of embodiment 3wherein treating the glutamate with the aldehyde is in the presence ofbase. Embodiment 65 provides methods of embodiment 64 where the base isdi(C₁-C₆ alkyl)amine, tri(C₁-C₆ alkyl)amine, tri(hydroxy C₁-C₆alkyl)amine, tetra(C₁-C₆ alkyl)guanidine, quinuclidine, pyridine,imidazole, or alkylimidazole. In embodiment 66, the base istriethylamine.

Embodiment 67 provides methods of embodiment 64 where the base is aninorganic base. In embodiment 68, the method of embodiment 67 is wherethe inorganic base is sodium carbonate.

Embodiment 69 provides method according to any one of embodiments 3 or64-68 wherein treating the glutamate with the aldehyde is at temperaturebetween about 0 to about 30° C. In embodiment 70, temperature is betweenabout 5 to about 20° C. In embodiment 71, temperature is about 5 toabout 10° C.

Embodiment 72 provides method according to any one of embodiments 3 or64-71 wherein treating the glutamate with the aldehyde is done up to 2hours.

In embodiment 73, the disclosure provides methods according to any oneof embodiments 3 or 64-72 where treating the glutamate with the aldehydeis in the presence of a catalyst and hydrogen gas. Embodiment 74provides methods of embodiment 73 where the catalyst is a palladiumcatalyst. For example the palladium catalyst is Pd/C. Embodiment 75provides methods of embodiment 73 where the catalyst is Raney nickel.Other suitable catalysts include rhodium, platinum, and rutheniumcatalysts.

In embodiment 76, the disclosure provides methods according to any oneof embodiments 3 or 73-75 wherein treating the glutamate with thealdehyde is in the presence of the catalyst and the hydrogen gas is attemperature between about 10 to about 30° C. In embodiment 77, thetemperature is about 20° C.

Embodiment 78 provides methods of embodiment 76 or 77 where treating isat pressure of about 450 psi to about 650 psi.

In embodiment 79, the disclosure provides methods according to any oneof embodiments 3 or 64-78 optionally comprising a heating step aftertreating the glutamate with the aldehyde is in the presence of thecatalyst and the hydrogen gas. In embodiment 80, the heating step is attemperature between about 50 to about 120° C. In embodiment 81, theheating step is at temperature about 90° C. In embodiment 82, theheating step is at pressure of about 500 psi to about 800 psi.

Embodiment 83 provides methods according to embodiment 79, wherein theheating step is at temperatures below 90° C. Such embodiment mightprovide the compositions of embodiment 59 or 60.

Embodiment 84 provides methods according to any one of embodiments 3 or64-83, wherein treating the glutamate with the aldehyde is in thepresence of solvent or mixture of solvents. Suitable solvents include,but are not limited to, water, alcohols, glycols, organic proticsolvents, organic aprotic solvents, or mixture thereof. In embodiment85, the solvent is water, alcohol, or glycol, or mixture thereof.Embodiment 86 provides methods where the solvent is methanol, ethanol,propanol, isopropanol, or butanol, or mixture thereof. In embodiment 87,the solvent is methanol, ethanol, or mixture thereof.

In embodiment 88, the disclosure provides methods according to any oneof embodiments 3 or 64-87 wherein R₁₃ is C₁-C₂₃ alkyl or C₂-C₂₃ alkenyl,each optionally substituted with one or more of R₁₅. In embodiment 89,the disclosure provides methods of embodiment 88 wherein R₁₃ is C₄-C₁₆alkyl optionally substituted with one or more of R₁₅. In embodiment 90,the disclosure provides methods of embodiment 88 wherein R₁₃ is nonyloptionally substituted with one or more of R₁₅. Thus, embodiment 90provides aldehyde which is decanal. In embodiment 91, the disclosureprovides methods of embodiment 88 wherein R₁₃ is C₄-C₁₆ alkenyloptionally substituted with one or more of R₁₅. Embodiment 92 providesaldehyde which is 2-propyl-2-heptenal, geranial, or citral.

Embodiment 93 provides methods according to any one of embodiments 3 or64-87, wherein at least a portion of the aldehyde is the product ofin-situ aldol condensation between two aldehydes, which may be the sameor different. Such embodiment might also provide the compositions ofembodiment 56 or 57. In embodiment 94, when in-situ aldol condensationis performed in the presence of the glutamate, the method provides amixture of two or more compounds of formula (IV). In embodiment 95, thedisclosure provides a method according to according to any one ofembodiments 3 or 64-94, wherein one compound of formula (IV) has R₁₂that is branched C₃-C₂₄ alkyl, branched C₄-C₂₄ alkenyl, or branchedC₄-C₂₄ alkynyl, each optionally substituted with one or more of R₁₅.

Embodiment 96 provides methods according to embodiment 93, wherein thealdehyde is the product of complete in-situ aldol condensation (>90%conversion) between two aldehydes, which may be the same or different,and that at least one of them is enolizable. Suitable aldehydes preparedfrom this embodiment include but are not limited to α,β-unsaturatedaldehydes (for example, 2-propyl-2-heptenal.)

Embodiment 97 provides methods according to any one of embodiments 3 or64-87, wherein at least a portion of the aldehyde is derived from anyfunctionalization of olefins, before treating the glutamate with thealdehyde. Functionalization method includes, but not limited to,hydroformylation of olefins. Olefins can be alkenes that are mono-, di-,or tri-substituted with R₁₅, or conjugated diene with any degree ofsubstitution. Examples of olefins suitable for functionalizationinclude, but not limited to, 1-octene, 4-octene, 2-methyl-propene,myrcene, and farnesene.

Embodiment 98 provides methods according to any one of embodiments 3 or64-87, wherein the aldehyde can be naturally-derived,petrochemically-derived, or in-situ generated. Non-limiting examples ofnaturally-derived aldehydes include 3-ethyl-7,11-dimethyldodecanal,geranial, 1-nonanal, and decanal. Non-limiting example ofpetrochemically-derived aldehyde includes 2-propyl-2-heptenal. Exampleof in-situ generated aldehyde during the reaction with glutamic acidincludes, but not limited to, 2-octyl-dodecanal generated in situ froman aldol condensation of decanal.

Embodiment 99 provides methods according to any one of embodiments 3 or64-98, wherein only one compound of formula (IV) is prepared.

Embodiment 100 provides methods according to any one of embodiments 3 or64-98, wherein a mixture of two compounds of formula (IV) is prepared.In embodiment 101, the method according to embodiment 100 provides amixture wherein one compound has R₁₂ that is unbranched C₃-C₂₄ alkyl,and other compound has R₁₂ that is branched C₃-C₂₄ alkyl.

Embodiment 102 provides methods according to any one of embodiments 3 or64-101, wherein the method also produces a compound of formula (IV) or amixture of one or more compounds of formula (IV) and a compound offormula (III).

Compositions and Dosage

In another aspect, the present disclosure provides compositionscomprising one or more compounds with respect to formulae (I)-(IV) andan additive, excipient or diluent. The exact nature of the additive,excipient or diluent will depend upon the desired use for thecomposition. Examples, include, but are not limited to: other cleaningagents (e.g. surfactants, co-surfactants), chelating agents, pH controlagents, enzymes, alkalinity sources, thickeners, soil release polymers,defoamers, dispersant polymers, hydrotropes, antibacterial actives,agents, bleaching agents, aesthetic enhancing agents (i.e., dyes,colorants, pigments, perfumes, etc.), oils, solvents, binders, fillers,carrier mediums, pharmaceutically active compounds (e.g., antiviralagents, antitumor agents, antihistamine agents, gene therapy agents,etc.), agrochemically active compounds (e.g., glyphosate, dicamba,2-4-dichloroacetic acid, etc.), and mixtures thereof.

In particular, the present disclosure provides shampoo and bodywashformulation compositions comprising one or more compounds with respectto formulae (I)-(IV), and one or more of: an anionic (amphoteric, ornonionic surfactant. Anionic surfactants include, but are not limited tosulfates, sulphonates, sulphosuccinates, Isethionates, taurates, etc.Amphoteric surfactants include, but are not limited to betaine,amphoacetate, etc. Nonionic surfactants include, but are not limited toalcohol ethoxylates, amine oxide, etc.

Suitable surfactants are described in Handbook of Surfactants publishedby Blackie Academic & Professional. The compositions of the disclosuremay also comprise: rheology modifiers such as ASE (alkali-solubleemulsion), HASE (Hydrophobically modified alkali-soluble emulsion). HEC(Hydroxyethyl Cellulose), HPMC (Hydroxypropyl methyl cellulose), MC(methyl cellulose), CMC (carboxy methyl cellulose), starch, clay, orother natural polymers. Acrylic rheology modifiers include, but are notlimited to, Acrylates/Steareth-20 Methacrylate Copolymer,Acrylates/Beheneth-25 Methacrylate Copolymer, Acrylates Copolymer,PEG-150/Decyl Alcohol/SMDI Copolymer, PEG-150/Stearyl Alcohol/SMDICopolymer, PEG-150/Distearate, Acrylates/Steareth-20 MethacrylateCrosspolymer, Acrylates/Vinyl Neodecanoate Crosspolymer, and xanthangum.

The composition may optionally include one or more additional compounds.

The compound(s) described herein, or compositions thereof, willgenerally be used in an amount effective to achieve the intended result.Dosage amounts will typically be in the range of from about 0.01 toabout 100 weight %, or about 1 to about 99 weight %, but may be higheror lower, depending upon, among other factors, the activity as asurfactant, if the material is used as the main active surfactant andvarious other factors. Skilled artisans will be able to optimizeeffective dosages without undue experimentation.

A composition of the disclosure may be used in any suitable productform. Suitable product forms include, but not limited to: solids,granules, powders, liquids, gels, pastes, semi-solids, tablets,water-soluble pouches, and combinations thereof. The composition mayalso be packaged in any suitable form, for example, in a kit.

DEFINITIONS

The following terms and expressions used have the indicated meanings.Terms used herein may be preceded and/or followed by a single dash, “—”,or a double dash, “≡”, to indicate the bond order of the bond betweenthe named substituent and its parent moiety; a single dash indicates asingle bond and a double dash indicates a double bond. “≡” means asingle or double bond. In the absence of a single or double dash it isunderstood that a single bond is formed between the substituent and itsparent moiety; further, substituents are intended to be read “left toright” unless a dash indicates otherwise. For example,C₁-C₆alkoxycarbonyloxy and —OC(O)C₁-C₆alkyl indicate the samefunctionality; similarly arylalkyl and -alkylaryl indicate the samefunctionality.

The term “alkenyl” as used herein, means a straight or branched chainhydrocarbon containing from 2 to 20 carbons, unless otherwise specified,and containing at least one carbon-carbon double bond. Representativeexamples of alkenyl include, but are not limited to, ethenyl,2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl,2-heptenyl, 2-methyl-1-heptenyl, 3-decenyl, and3,7-dimethylocta-2,6-dienyl, and 2-propyl-2-heptenyl.

The term “alkoxy” as used herein, means an alkyl group, as definedherein, appended to the parent molecular moiety through an oxygen atom.Representative examples of alkoxy include, but are not limited to,methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentyloxy, andhexyloxy.

The term “alkyl” as used herein, means a straight or branched chainhydrocarbon containing from 1 to 20 carbon atoms unless otherwisespecified. Representative examples of alkyl include, but are not limitedto, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl,tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl,2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, andn-decyl.

The term “alkynyl” as used herein, means a straight or branched chainhydrocarbon group containing from 2 to 10 carbon atoms unless otherwisespecified, and containing at least one carbon-carbon triple bond.Representative examples of alkynyl include, but are not limited, toacetylenyl, 1-propynyl, 2-propynyl, 3-butynyl, 2-pentynyl, and1-butynyl.

The term “aryl,” as used herein, means a phenyl (i.e., monocyclic aryl),or a bicyclic ring system containing at least one phenyl ring or anaromatic bicyclic ring containing only carbon atoms in the aromaticbicyclic ring system. The bicyclic aryl can be azulenyl, naphthyl, or aphenyl fused to a monocyclic cycloalkyl, a monocyclic cycloalkenyl, or amonocyclic heterocyclyl. The bicyclic aryl is attached to the parentmolecular moiety through any carbon atom contained within the phenylportion of the bicyclic system, or any carbon atom with the napthyl orazulenyl ring.

An “aralkyl” or “arylalkyl” group comprises an aryl group covalentlyattached to an alkyl group, either of which independently is optionallysubstituted. Preferably, the aralkyl group is aryl(C₁-C₆)alkyl,including, without limitation, benzyl, phenethyl, and naphthylmethyl.

The terms “cyano” and “nitrile” as used herein, mean a —CN group.

The term “cycloalkyl” as used herein, means a monocyclic or a bicycliccycloalkyl ring system. Monocyclic ring systems are cyclic hydrocarbongroups containing from 3 to 8 carbon atoms, where such groups can besaturated or unsaturated, but not aromatic. In certain embodiments,cycloalkyl groups are fully saturated. Examples of monocycliccycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl,cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. Representativeexamples of bicyclic ring systems include, but are not limited to,bicyclo[3.1.1]heptane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane,bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane, and bicyclo[4.2.1]nonane.

The term “halogen” as used herein, means —Cl, —Br, —I or —F.

The terms “haloalkyl”, “haloalkenyl” and “haloalkoxy” refer to an alkyl,alkenyl or alkoxy group, as the case may be, which is substituted withone or more halogen atoms.

The term “heteroaryl,” as used herein, means a monocyclic heteroaryl ora bicyclic ring system containing at least one heteroaromatic ring. Themonocyclic heteroaryl can be a 5 or 6 membered ring. The 5 membered ringconsists of two double bonds and one, two, three or four nitrogen atomsand optionally one oxygen or sulfur atom. The 6 membered ring consistsof three double bonds and one, two, three or four nitrogen atoms. The 5or 6 membered heteroaryl is connected to the parent molecular moietythrough any carbon atom or any nitrogen atom contained within theheteroaryl. The bicyclic heteroaryl consists of a monocyclic heteroarylfused to a phenyl, a monocyclic cycloalkyl, a monocyclic cycloalkenyl, amonocyclic heterocyclyl, or a monocyclic heteroaryl. Representativeexamples of heteroaryl include, but are not limited to, furyl,imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyrrolyl, tetrazolyl,thiadiazolyl, thiazolyl, thienyl, triazolyl, triazinyl, benzimidazolyl,benzofuranyl, benzothienyl, benzoxadiazolyl, benzoxathiadiazolyl,benzothiazolyl, cinnolinyl, 5,6-dihydroquinolin-2-yl,5,6-dihydroisoquinolin-1-yl, furopyridinyl, indazolyl, indolyl,isoquinolinyl, naphthyridinyl, quinolinyl, or purinyl.

The term “heterocyclyl” as used herein, means a monocyclic heterocycleor a bicyclic heterocycle. The monocyclic heterocycle is a 3, 4, 5, 6 or7 membered ring containing at least one heteroatom independentlyselected from the group consisting of 0, N, and S where the ring issaturated or unsaturated, but not aromatic. The 3 or 4 membered ringcontains 1 heteroatom selected from the group consisting of O, N and S.The 5 membered ring can contain zero or one double bond and one, two orthree heteroatoms selected from the group consisting of 0, N and S. The6 or 7 membered ring contains zero, one or two double bonds and one, twoor three heteroatoms selected from the group consisting of O, N and S.The bicyclic heterocycle is a monocyclic heterocycle fused to either aphenyl, a monocyclic cycloalkyl, a monocyclic cycloalkenyl, a monocyclicheterocycle, or a monocyclic heteroaryl. Representative examples ofheterocycle include, but are not limited to, aziridinyl, diazepanyl,1,3-dioxanyl, 1,3-dioxolanyl, 1,3-dithiolanyl, 1,3-dithianyl,imidazolinyl, imidazolidinyl, isothiazolinyl, isothiazolidinyl,isoxazolinyl, isoxazolidinyl, morpholinyl, oxadiazolinyl,oxadiazolidinyl, oxazolinyl, oxazolidinyl, piperazinyl, piperidinyl,pyranyl, pyrazolinyl, pyrazolidinyl, pyrrolinyl, pyrrolidinyl,tetrahydrofuranyl, tetrahydrothienyl, thiadiazolinyl, thiadiazolidinyl,thiazolinyl, thiazolidinyl, thiomorpholinyl, 1,1-dioxidothiomorpholinyl(thiomorpholine sulfone), thiopyranyl, trithianyl,2,3-dihydrobenzofuran-2-yl, and indolinyl.

The phrase “one or more” substituents, as used herein, refers to anumber of substituents that equals from one to the maximum number ofsubstituents possible based on the number of available bonding sites,provided that the above conditions of stability and chemical feasibilityare met. Unless otherwise indicated, an optionally substituted group mayhave a substituent at each substitutable position of the group, and thesubstituents may be either the same or different. As used herein, theterm “independently selected” means that the same or different valuesmay be selected for multiple instances of a given variable in a singlecompound.

“Optional” or “optionally” means that the subsequently described eventor circumstance may or may not occur, and that the description includesinstances where said event or circumstance occurs and instances in whichit does not. One of ordinary skill in the art would understand that withrespect to any molecule described as containing one or more optionalsubstituents, only sterically practical and/or synthetically feasiblecompounds are meant to be included. “Optionally substituted” refers toall subsequent modifiers in a term, unless stated otherwise.

The term “polyoxyalkylene” refers to polymer moieties formed bypolymerizing or copolymerizing same or different alkylene oxide monomersto provide polymer moieties of desired size and weight, and the polymermoieties can be capped or uncapped. The polymer can be block or randompolymer, or both. In general, the alkylene oxide monomers areindependently straight or branched chain groups having from 1-8,preferably 2-5, carbon atoms.

Where the polymer moiety comprises two or more polyoxyalkylene groups,the individual polyoxyalkylene groups may be connected to each other bylinker groups. Examples of suitable linker groups are: —C(O), —O—,—OC(O)O—, —C(O)CH₂CH₂C(O)—, —S—S—, and —NR³—, where R³ is hydrogen, orC₁-C₆ alkyl. Non-limiting examples of polyoxyalkylene groups includepolyoxyethylene, a straight or branched chain polyoxypropylene, and astraight or branched chain polyoxybutylene. Polyoxyalkylene polymermoieties may have molecular weights of from about 80-10,000 Da; any ofthese moieties may be formed from several shorter, independently-sizedunits. The units may have molecular weights independently ranging fromabout 50 (i.e., one repeating unit of a polyethylene glycol), 80, 200,or 500 Da up to about 3000, 4000 or 5000 Da.

“Salt” refers to both acid and base addition salts. Non-limitingexamples of acid addition salts include those formed with inorganicacids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitricacid, phosphoric acid, and the like; as well as organic acids such asacetic acid, trifluoroacetic acid, propionic acid, lactic acid, oxalicacid, maleic acid, malonic acid, succinic acid, and the like.Non-limiting examples of base addition salts include those formed whenan acidic proton present in the parent compound is replaced by a metalion, such as sodium, potassium, lithium, ammonium, calcium, magnesium,iron, zinc, copper, manganese, aluminum salts, and the like. Saltsderived from organic bases include, but are not limited to, salts ofprimary, secondary, and tertiary amines, substituted amines includingnaturally occurring substituted amines, cyclic amines and basic ionexchange resins. Examples of organic bases include triethylamine,ethanolamine, triethanolamine, guanidine, and choline.

The term “substituted”, as used herein, means that a hydrogen radical ofthe designated moiety is replaced with the radical of a specifiedsubstituent, provided that the substitution results in a stable orchemically feasible compound. The term “substitutable”, when used inreference to a designated atom, means that attached to the atom is ahydrogen radical, which can be replaced with the radical of a suitablesubstituent.

Methods of Preparation

The compounds of the present disclosure may be prepared by use of knownchemical reactions and procedures. Representative procedures for thepreparation of compounds of the disclosure are outlined below infollowing schemes. It is understood that the nature of the substituentsrequired for the desired target compound often determines the preferredmethod of synthesis. All variable groups of these methods are asdescribed in the generic description if they are not specificallydefined below.

Unless otherwise indicated, R₁₁, R₁₂, R₁₃, and R₁₄, and carry thedefinitions given in connection with formula (IV).

Those having skill in the art will recognize that the starting materialsand reaction conditions may be varied, the sequence of the reactionsaltered, and additional steps employed to produce compounds encompassedby the present disclosure, as demonstrated by the following examples.

Starting materials can be obtained from commercial sources includingrenewable sources, or prepared by well-established literature methodsknown to those of ordinary skill in the art. The reactions are performedin a solvent appropriate to the reagents and materials employed andsuitable for the transformations being affected. It will be understoodby those skilled in the art of organic synthesis that the functionalitypresent on the molecule should be consistent with the transformationsproposed. This will sometimes require a judgment to modify the order ofthe synthetic steps or to select one particular process scheme overanother in order to obtain a desired compound of the disclosure. In somecases, protection of certain reactive functionalities may be necessaryto achieve some of the above transformations. In general, the need forsuch protecting groups as well as the conditions necessary to attach andremove such groups will be apparent to those skilled in the art oforganic synthesis.

The disclosures of all articles and references mentioned in thisapplication, including patents, are incorporated herein by reference intheir entirety.

EXAMPLES

The preparation of the compounds of the disclosure is illustratedfurther by the following examples, which are not to be construed aslimiting the disclosure in scope or spirit to the specific proceduresand compounds described in them.

Equipment and Materials

An Autoclave Engineers 300 mL EZE-SEAL Reactor (Hast C) equipped withelectric jacketed heating is used with a 2-225 Kalrez 6375 O-ringgasket. A Control Tower operates the MagnaDrive stirring and controlswater cooling through an internal cooling loop via a water solenoidvalve. NMR spectra are acquired on a Bruker 400 MHz NMR system. Ultrahigh purity H₂ was supplied in cylinders by Michigan Airgas. The 5%Pd/Carbon Catalyst, 58.07% H₂O, is supplied by Johnson Matthey.

Example 1

Glutamic acid (3.7 g, 0.0251 mol), EtOH (10.5 g), and triethylamine (2.5g, 0.0247 mol) are added to a clean 100 mL, 3-neck round bottom flaskequipped with a magnetic stir bar, a N₂ bubbler, addition funnel,thermocouple, and an ice bath. The solution is maintained below 5° C.Farnesene aldehyde (5.0 g, 0.0213 mol) is loaded to the addition funneland added to the solution with good agitation while keeping the internaltemperature below 10° C. 5% Pd/C catalyst (1.204 g, water wet) isweighed and transferred into the 300 mL Autoclave reactor followed bywashing the premix solution into the reactor with EtOH (59.2 g). Thereactor is sealed and purged with N₂ three times at approximately 100psi with stirring, followed by a pressure check. The reactor is quicklyheated to 20° C. with stirring (813 rpm). H₂ is charged to the reactor,and pressure is set at approximately 561 psi. The reaction is carriedout for approximately 19 hours 57 minutes. The pressure is released anda reaction sample (˜2 mL) is withdrawn via syringe using the reactorsample port. The sample is filtered using a 0.45 μm Polypropylenesyringe filter (Whatman International, Ltd., Maidstone, England) andanalyzed by NMR. The analysis determined the transformation to theopen-chain N-alkyl glutamic acid derivative is nearly complete.

The reactor is then purged with 100 psi N₂ three times with stirring.The reactor is quickly heated to 90° C. with stirring (813 rpm). H₂ ischarged to the reactor, and pressure is set at approximately 751 psi.The reaction is carried out for approximately 21 hrs 23 minutes. Thesystem is cooled and H₂ vented. A reaction sample (˜2 mL) is withdrawnas previously described, filtered using a 0.45 μm Polypropylene syringefilter, and analyzed by NMR. The analysis determined the transformationto the pyroglutamate is sufficiently complete. The reaction mixture isdischarged from the reactor, and filtered using a 30 mL glass mediumfritted funnel and a celite bed. A small amount of glutamic acid-likecrystals are observed in the bottom of the reactor vessel whiletransferring the material to the filtercake. The bed is washed with anadditional 23 mL EtOH. Material (clear appearance) is transferred to a250 mL round bottom flask for further work-up.

The filtrate is then concentrated to a thick oil on the rotaryevaporator (bath temperature 45° C.). This is swirled in 50 mL ofhexanes, dissolving a majority of the oil. About 5 mL of pH 6.5, 1Mphosphate buffer solution is added. This resulted in two phases, thelargest is on the bottom. The bottom phase is drained off through alayer of filter aid in a coarse sintered glass funnel, with vacuumapplied to the filter flask, to remove some suspended crystallinesolids. The top phase (5-10 mL) is drained into a round bottom flask andconcentrated to dryness, giving about 1 g of a thick, tan oil. TLC(silica gel, 2 vol % 28% NH₃ in water/98 vol % EtOH, I₂ visualization)indicated a material with an R_(f) of about 0.85.

A small amount of hexanes is added back to the filtrate and the solutionis returned to the separatory funnel. The mixture is diluted with 50 mLof a 50/50 mix of MeOH and water. Two phases formed, the upper,primarily hexane. TLC of both phases showed that more of the materialhad been extracted into the hexane phase. An additional extraction ofthe MeOH/water phase is performed using 10 mL of hexanes. The combinedhexanes phases are concentrated on the rotary evaporator (Bath T=45° C.)to give approximately 1.5 g of a thick, light amber oil.

The lower, MeOH/water phase, is adjusted to pH 5 by addition of severalmL of 1M HCl. A pale viscous pink oil separates as a more dense phase.To the mixture is added 20 mL of CH₂Cl₂, the mixture is shaken briefly,and then allowed to settle a few minutes. The CH₂Cl₂ phase is drawn offand then concentrated to a viscous oil on the rotary evaporator (bathtemperature is 45° C.). The NMR spectra of a sample indicated that thereare two or more components. The material is then placed under full pumpvacuum (5 mmHg) for several hours (yield, 4.40 g). A small sample issubmitted for mass spectral characterization. The major component byLC/MS has an exact mass of 353.2930, C₂₁H₃₉NO₃. TLC of the remainingaqueous phase did not reveal any significant amounts of additionalcomponents. ¹H NMR (400 MHz, CDCl₃) δ 8.9 (br s, 1H), 4.21 (dd, J=9.0,3.1 Hz, 1H), 3.85-3.56 (m, 1H), 2.965-2.85 (m, 1H), 2.6-2.08 (m, 4H),1.72-1.42 (m, 3H), 1.4-1.0 (m, 16H), 0.95-0.75 (m, 12H). ¹³C NMR (100.6MHz, ¹H-decoupled, CDCl₃) δ 176.04, 174.86, 174.83, 59.89, 59.77, 40.05,39.35, 37.47, 37.38, 37.34, 36.91, 36.74, 33.46, 33.21, 32.76, 30.35,29.79, 27.96, 25.67, 25.59, 25.38, 25.29, 24.79, 24.78, 24.48, 24.11,23.97, 23.20, 22.71, 22.61, 19.67, 19.65, 10.73, 10.69, 10.48, 10.43.

Example 2

Glutamic acid (9.51 g, 0.0646 mol), MeOH (20.6 g), and triethylamine(13.1 g, 0.130 mol) are added to a clean 250 mL, 3-neck round bottomflask equipped with a magnetic stir bar, a N₂ bubbler, addition funnel,thermocouple and an ice bath. The solution is maintained below 5° C.2-Propylhept-2-enal (10.0 g, 0.0648 mol) is loaded to the additionfunnel and added to the solution with good agitation while keeping theinternal temperature below 10° C. 5% Pd/C catalyst (2.084 g, water wetas described in the general experimental) is weighed and transferredinto the 300 mL Autoclave reactor followed by washing the premixsolution into the reactor with MeOH (106.0 g). The reactor is sealed andpurged with N₂ three times at approximately 100 psi with stirring,followed by a pressure check. The reactor is quickly heated to 20° C.with stirring (806 rpm). H₂ is charged to the reactor, and pressure isset at approximately 586 psi. The reaction is carried out forapproximately 4 hrs 50 minutes. A reaction sample (˜2 mL) is extractedusing the reactor sample port, filtered using a 0.45 μm Polypropylenesyringe filter and analyzed by NMR, which shows a mixture of linear andcyclized structures. The reactor is purged with 100 psi N₂ three timeswith stirring. The reaction is then continued at an elevated temperatureand pressure. The reactor is quickly heated to 90° C. with stirring (806rpm). H₂ is charged to the reactor, and pressure is set at approximately809 psi. The reaction is carried out for approximately 18 hours 41minutes. The system is cooled and H₂ vented. A reaction sample (˜2 mL)is extracted using the reactor sample port, filtered using a 0.45 μmPolypropylene syringe filter and analyzed by NMR. The analysisdetermined the transformation to the pyroglutamate is essentiallycomplete. The reaction mixture is discharged from the reactor, andfiltered using a 60 mL glass medium fritted funnel and a celite bed. Thebed is washed with an additional 10 mL MeOH. Material (clear,non-colored appearance) is transferred to a 250 mL round bottom flaskfor further work-up.

The filtrate is concentrated to a thick oil on the rotary evaporator(bath temperature 45° C.) and then put on the vacuum pump overnight togive 13.2 g of a faint pink oil. This is dissolved in 50 mL of MeOH. 50mL of de-ionized water containing 2.0 g (0.05 mol) of sodium hydroxidepellets is added and the solution is transferred to a 125 mL separatoryfunnel and extracted with 3×20 mL of hexanes. The aqueous MeOH phase isthen acidified (pH<3) with 5.0 g of 37% HCl. Two phases formed. To themixture is added 20 mL of CH₂Cl₂, the mixture is shaken briefly, andthen allowed to settle a few minutes. The CH₂Cl₂ phase is drawn off andthe aqueous MeOH is extracted with additional CH₂Cl₂ (2×20 mL). TheCH₂Cl₂ extracts are combined and concentrated to a viscous oil on therotary evaporator (bath temperature is 45° C.). The pale violet oil isplaced under full pump vacuum overnight with gentle warming (30-40° C.)and stirring. The oil crystallized (11.0 g). NMRs (¹³C— & ¹H—) showedthat the material is substantially free of triethylamine. ¹H NMR (400MHz, CDCl₃) δ 10.76 (br s, 1H), 4.21 (ddd, J=9.1, 2.5, 1.0 Hz, 1H), 3.67(ddd, J=13.9, 9.4, 2.0 Hz, 1H), 2.84 (ddd, J=14.0, 5.1, 2.5 Hz, 1H),2.65-2.24 (m, 3H), 2.18 (ddt, J=12.8, 9.3, 3.1 Hz, 1H), 1.70-1.56 (m,1H), 1.42-1.1 (m, 12H), 0.92-0.82 (m, 6H). ¹³C NMR (100.6 MHz,¹H-decoupled, CDCl₃) δ 176.99, 174.54, 60.00, 45.99, 35.32, 33.92,33.59, 32.18, 31.60, 31.25, 29.60, 26.13, 25.73, 23.14, 22.57, 19.69,19.23, 14.42, 14.36, 14.04.

Example 3

Glutamic acid (10.0 g, 0.068 mol), MeOH (20.7 g), and triethylamine(12.95 g, 0.128 mol) are added to a clean 250 mL, 3-neck round bottomflask equipped with a magnetic stir bar, a N₂ bubbler, addition funnel,thermocouple and an ice bath. The solution is maintained below 5° C.Decanal (10.1 g, 0.0646 mol) is loaded to the addition funnel and addedto the solution with good agitation while keeping the internaltemperature below 10° C. The mixture at this stage had a slight yellowappearance. 5% Pd/C catalyst (2.008 g, water wet) is weighed andtransferred into the 300 mL Autoclave reactor followed by washing thepremix solution into the reactor with MeOH (105.8 g). The reactor issealed and purged with N₂ three times at approximately 100 psi withstirring, followed by a pressure check. The reactor is quickly heated to20° C. with stirring (807 rpm). H₂ is charged to the reactor, andpressure is set at approximately 551 psi. The reaction is carried outfor approximately 5 hrs 32 minutes. A reaction sample (˜2 mL) isextracted using the reactor sample port, filtered using a 0.45 μmPolypropylene syringe filter and analyzed by NMR. The analysisdetermined the transformation to the open chain N-alkylglutamic acid isnearly complete and the reaction is continued at an elevated temperatureand pressure. NMR spectral data on a sample of the open-chain glutamicacid derivative: ¹H NMR (400 MHz, CDCl₃) δ 4.75 (br s, 3H), 3.4 (m, 1H),2.8 (m, 2H), 2.55-2.3 (m, 2H), 2.15-2.0 (m, 2H), 1.75-1.6 (m, 1H),1.5-1.1 (br m, 23H), 0.95-0.70 (m, 4.5H). ¹³C NMR (100.6 MHz, ¹Hdecoupled, CDCl₃) δ 179.60, 172.56, 51.85, 45.84, 36.29, 35.44, 31.87,31.84, 31.31, 31.24, 29.84, 29.61, 29.58, 29.52, 29.30, 29.26, 26.36,26.20, 22.64, 22.62, 14.05.

The reactor is purged with 100 psi N₂ three times with stirring. Thereactor is quickly heated to 90° C. with stirring (807 rpm). H₂ ischarged to the reactor, and pressure is set at approximately 702 psi.The reaction is carried out for approximately 18 hrs 41 minutes. Thesystem is cooled and H₂ vented. A reaction sample (˜2 mL) is extractedusing the reactor sample port, filtered using a 0.45 μm Polypropylenesyringe filter and analyzed by NMR. The analysis determined thetransformation to the N-alkylpyroglutamic acid is effectively complete.The reaction mixture is discharged from the reactor, and filtered usinga 60 mL glass medium fritted funnel and a celite bed. The bed is washedwith an additional 10 mL MeOH. Material (clear, non-colored appearance)is transferred to a 250 mL round bottom flask for further work-up.

The filtrate is concentrated to a thick oil (approximately 20 g) on therotary evaporator (bath temperature 45° C.). This is dissolved in 50 mLof MeOH. A white crystalline precipitate formed, is filtered off, andwashed with ˜20 mL of MeOH. This is identified as glutamic acid by¹H-NMR. The MeOH filtrate is then treated with 18 g of 15 wt % sodiumhydroxide and 32 g of deionized water. The basic solution is extractedwith 20 mL of hexanes in a 125 mL separatory funnel. CH₂Cl₂ (20 mL) isadded, resulting in a homogeneous solution. This solution is thenextracted with another 20 mL of hexanes. The aqueous MeOH phase is thenacidified (pH<3) with 13.25 g of 37% HCl, and two phases formed. Themixture is extracted with 3×20 mL of CH₂Cl₂. The CH₂Cl₂ extracts arecombined and concentrated on the rotary evaporator. The thick pink syrupis then placed under full pump vacuum overnight with stirring andheating to about 30-40° C. The weight of product obtained is 11.81 g andthe weight of recovered (air dried) glutamic acid is 1.87 g.

¹H-NMR showed that this material still contained significant amounts oftriethylamine. It is thus combined with another small batch of crudemixture prepared in a similar manner. These two batches are dissolvedwith stirring in 50 mL of MeOH. Deionized H₂O (50 mL) containing 2.33 g(0.0583 mol) of sodium hydroxide is added and the solution is stirred atroom temperature over the weekend. The solution is poured into a 250 mLseparatory funnel and extracted with hexanes (3×20 mL), allowing about20 min settling time for each extraction. The basic solution isacidified with 5.88 g of 37% HCl to pH<3. The acidified, 2-phase mixtureis diluted with 20 mL of CH₂Cl₂. The CH₂Cl₂ product phase is drawn offand the aqueous solution is extracted with additional CH₂Cl₂ (2×20 mL).The combined CH₂Cl₂ extracts are concentrated to a thick oil on therotary evaporator (bath temperature is 45° C.) and then placed underfull pump vacuum overnight with stirring and heating to about 30-40° C.to remove residual solvents. The recovered weight of material is 13.96g. ¹H— and ¹³C-NMR spectra showed that the material is substantiallyfree of triethylamine (0.2 wt %) and the material is an approximately43.3:56.7 molar mixture of the C₁₀ and C₂₀ N-alkyl pyroglutamic acids(35:65 wt. ratio). LC/MS m/s [M+H]⁺ 410.36 (exact mass 409.36,C₂₅H₄₇NO₃) and 270.21 (exact mass 269.20, C₁₅H₂₇NO₃). A small amount ofthe open chain C₂₀ compound is also observed by LC/MS with [MH]+ of428.3757 (exact mass 427.37, C₂₅H₄₉NO₄).

Example 4

Glutamic acid (10.9 g, 0.0741 mol), MeOH (25.0 g), and triethylamine(15.30 g, 0.1512 mol) are added to a clean 500 mL, 3-neck round bottomflask equipped with a magnetic stir bar, a N₂ bubbler, addition funnel,thermocouple, and an ice bath. The solution is maintained below 5° C.Decanal (17.5 g, 0.112 mol) is loaded to the addition funnel and addedto the solution with good agitation while keeping the internaltemperature below 10° C. The mixture is stirred for ˜1.5 hours. At thisstage, the premix had a slight yellow appearance. 5% Pd/C catalyst (2.08g, water wet) is weighed and transferred into the 300 mL Autoclavereactor followed by washing the premix solution into the reactor withMeOH (91.0 g). The reactor is sealed and purged with N₂ three times atapproximately 100 psi with stirring, followed by a pressure check. Thereactor is quickly heated to 20° C. with stirring (811 rpm). H₂ ischarged to the reactor, and pressure is set at approximately 500 psi.The reaction is carried out for approximately 2 hours 28 minutes. Thereactor is vented of H₂ prior to continuing at an elevated temperatureand pressure. The reactor is quickly heated to 90° C. with stirring (811rpm). H₂ is charged to the reactor, and pressure is set at approximately701 psi. The reaction is carried out for approximately 20 hrs. Thesystem is cooled, H₂ vented and N₂ purged through the reactor beforedischarging the contents. The reaction mixture is filtered using a 60 mLglass medium fritted funnel and a celite bed. The bed is washed with anadditional 20 mL MeOH. Material is observed to have a clear, slightlyyellowed appearance. No crystals are observed in the bottom of thereactor when transferring to the filter. Only a small thin ring of whitecrystal-like material is observed at the solvent stirring level in thereactor. The filtered material is transferred to a 500 mL round bottomflask for further work-up.

The filtrate (144.33 g) is concentrated to a thick oil (approximately 25g) on the rotary evaporator (bath temperature 45° C.). Upon cooling somewhite crystalline solids are deposited (glutamic acid). The oily residueis dissolved in 50 mL of MeOH and combined with a second batch of crudematerial in 50 mL of MeOH prepared in a similar manner. The combinedMeOH solutions are diluted with 100 mL of water containing 6.0 g ofsodium hydroxide pellets and transferred into a 500 mL separatoryfunnel. The basic solution is extracted with 100 mL of hexanes and thenwith 3×50 mL of hexane. About 40 mL of hexane stayed dissolved in thebasic aqueous MeOH mixture. The aqueous MeOH phase is then acidified(pH<3) with 15.8 g of 37% HCl. Two phases formed, an upper hexane phase(yellow) containing the N-alkyl pyroglutamic acid and a lower aqueousphase. After separation of the upper phase, the aqueous phase isextracted with 2×50 mL of CH₂Cl₂. The CH₂Cl₂ extracts are colorless. Thewarm aqueous MeOH phase is set aside and allowed to cool. A significantamount of white crystals separated (glutamic acid). The CH₂Cl₂ extractsare combined with the hexane phase and washed once with about 25 mL ofwater. After letting the phases separate, the organic phase isconcentrated on the rotary evaporator. The thick pale yellow syrup isthen placed under full pump vacuum overnight with stirring and heatingto about 30-40° C. to remove residual solvents. The weight of productobtained is 33.87 g. ¹H-NMR analysis showed that it is 92.64 wt % C₂₀N-alkyl pyroglutamic acid, 6.50 wt % C₁₀ N-alkyl pyroglutamic acid, 0.84wt % Et₃N, and 0.02 wt % CH₂Cl₂. ¹H NMR (400 MHz, CDCl₃) δ 8.78 (br s,1H), 4.21 (d, J=3.2 Hz, shoulder), 4.17 (dd, J=9.0, 2.5 Hz, 1H),3.81-3.71 (m, shoulder), 3.66 (dd, J=13.9, 9.5 Hz, 1H), 2.91 (ddd,J=13.8, 8.6, 5.4 Hz, 0.106H), 2.77 (dd, J=13.9, 5.2 Hz, 0.995H),2.69-2.23 (m, 3H), 2.23-1.99 (m, 1H), 1.62 (s, 1H), 1.55-1.0 (br s,32H), 0.88 (t, J=6.7 Hz, 6H). ¹³C NMR (100.6 MHz, ¹H-decoupled, CDCl₃) δ176.52, 176.24, 175.25, 60.17, 59.89, 45.94, 45.46, 41.97, 35.58, 31.91,31.69, 31.18, 30.07, 30.04, 29.68, 29.67, 29.65, 29.61, 29.56, 29.35,29.33, 29.31, 27.05, 26.95, 26.50, 26.11, 23.25, 22.67, 14.10.

Example 5

Glutamic acid (10.9 g, 0.0741 mol), MeOH (25.23 g), and triethylamine(16.60 g, 0.1640 mol) are added to a clean 500 mL, 3-neck round bottomflask equipped with a magnetic stir bar, a N₂ bubbler, addition funnel,thermocouple and an ice bath. The solution is maintained below 5° C.Decanal (17.5 g, 0.112 mol) is loaded to the addition funnel and addedto the solution with good agitation while keeping the internaltemperature below 10° C. The mixture is stirred for approximately ˜1hour total, including loading the premix into the reactor and completingthe N₂ purge step. The reactor vessel bottom is chilled in a bucket ofice. The premix, at the time of transfer, had only a slight yellowcreamy appearance. 5% Pd/C catalyst (2.14 g, water wet) is weighed andtransferred into the 300 mL Autoclave reactor followed by washing thepremix solution into the reactor with MeOH (94.0 g). The reactor issealed and purged with N₂ three times at approximately 100 psi withstirring, followed by a pressure check. The reactor is quickly heated to20° C. with stirring (806 rpm). H₂ is charged to the reactor, andpressure is set at approximately 583 psi. The reaction is carried outfor approximately 5 hours 41 minutes. The reactor is vented of H₂ priorto continuing at an elevated temperature and pressure. The reactor isquickly heated to 90° C. with stirring (806 rpm). H₂ is charged to thereactor, and pressure is set at approximately 726 psi. The reaction iscarried out for approximately 24 hours 5 minutes. The system is cooled,H₂ vented and N₂ purged through the reactor before discharging thecontents. The reaction mixture is filtered using a 60 mL glass mediumfritted funnel and a celite bed. The bed is washed with an additional 20mL MeOH. Material is observed to have a clear, slightly yellowedappearance. No crystals are observed in the bottom of the reactor whentransferring to the filter. Only a small thin ring of white crystal-likematerial is observed at the solvent stirring level in the reactor. Thefiltered material is transferred to a 500 mL round bottom flask forfurther work-up.

The filtrate (177.3 g) is concentrated to a thick oil (approximately 26g) on the rotary evaporator (bath temperature 45° C.). Upon cooling,unlike in example 4, the thick, nearly colorless syrup did not depositany solids. The syrup is dissolved in 50 mL of MeOH then diluted with 50mL of water containing 3.1 g of sodium hydroxide pellets. The solutionis transferred into a 500 mL separatory funnel and extracted with 100 mLof hexanes. This is followed with extractions with 3×50 mL of hexanes.The aqueous MeOH phase is then acidified (pH<3) with 7.9 g of 37% HCl.Two phases formed, an upper hexane phase (pale yellow) containing theN-alkyl pyroglutamic acid and a lower aqueous phase. After separation ofthe upper phase, the aqueous phase is extracted with 2×25 mL of CH₂Cl₂.The CH₂Cl₂ extracts are combined with the hexane phase and the combinedorganics are concentrated on the rotary evaporator. The thick paleyellow syrup (21.75 g) is then placed under full pump vacuum overnightwith stirring and heating to about 30-40° C. to remove residualsolvents. The weight of product obtained is 20.81 g (85% yield). ¹H-NMRanalysis showed that it is 50.60 wt % C₂₀ N-alkyl pyroglutamic acid,48.74 wt % C₁₀ N-alkyl pyroglutamic acid, and 0.65 wt % Et₃N. ¹H NMR(400 MHz, CDCl₃) δ 10.61 (br s, 1H), 4.22 (ddd, J=13.4, 9.2, 2.8 Hz,1H), 3.80-3.63 (m, 1H), 2.95 (ddd, J=14.0, 8.8, 5.4 Hz, 0.63H), 2.81(dd, J=14.0, 5.3 Hz, 0.44H), 2.65-2.28 (m, 2H), 2.22-2.12 (m, 1H),1.8-1.4 (m, 2H), 1.25 (br s, 23H), 0.88 (dd, J=7.0, 6.5 Hz, 4.5H). ¹³CNMR (100.6 MHz, ¹H-decoupled, CDCl₃) δ 176.81, 176.51, 174.72, 59.96,59.66, 46.02, 42.13, 35.56, 31.90, 31.87, 31.65, 31.23, 30.01, 29.65,29.60, 29.52, 29.42, 29.35, 29.28, 26.99, 26.90, 26.48, 26.11, 23.17,23.11, 22.66, 14.09.

Example 6 Preparation of Larger Batch of C₁₀/C₂₀ Pyroglutamic Acid

A large batch of N—C₁₀/C₂₀ pyroglutamic acid prepared as described inExample 5 is dissolved in 50 mL of CH₂Cl₂ and is filtered through amedium frit glass funnel to remove some insoluble material. The filtrateis concentrated to a thick oil on the rotary evaporator (bathtemperature 45° C.). After holding the material (with stirring)overnight at 35° C. under a full pump vacuum to remove residual solvent,the weight of product obtained is 38.78 g. ¹H-NMR analysis gave thefollowing composition: 47.77 wt % C₁₀ N-alkyl pyroglutamic acid, 51.52wt % C₂₀ N-alkyl pyroglutamic acid, 0.57 wt % Et₃N, and 0.14 wt %CH₂Cl₂.

Example 7 Critical Micelle Concentration

The critical micelle concentration (Kibron CMC) and surface tension ofthe N-alkyl pyroglutamic acids (as Na⁺ salts) and related commercialsurfactants were evaluated. For each sample, a total of twelve dilutionsstarting at 1 wt % were prepared, reducing the concentration in eachdilution by half by taking an aliquot of the previous dilution andadding the same amount of water. The surface tension of all 12 dilutionswas measured using a Kibron Delta-8 multichannel microtensiometer.Sample volume for each analysis was 50 μL. Results were summarized inTable 1.

TABLE 1 Sodium Salt Properties Product of Kibron Surface Tension ExampleNo. CMC (ppm) (1%) Dynes/cm Shake Foam t = 0 (mL) 1 625 38 36 2 >1000034 11 3 78 28 34 4 78 29 29 6 78 29 38

All alkyl pyroglutamates in Table 1 can reduce the surface tension ofwater to 30-40 dynes/cm at 1 wt % solid. This is typical for commonanionic surfactants such as sodium laureth sulfate.

Example 8 Foam Height Analysis

Foaming profile of the N-alkyl pyroglutamates are evaluated using ashake foam test, and evaluated against sodium laureth sulfate. For eachsample, a 0.1 wt % solution is prepared by diluting 50 mg active to 50 gin water. The 0.1 wt % solution is added to a 100 mL graduated cylinderand capped. The cylinder is shaken by hand 20 times, each time thecylinder is inverted and brought back to an upright position. Foamheight (in mL) is defined as the highest point of the top layer of thefoam in the graduated cylinder. If the top of the foam was not flat, themidpoint of the top of the foam was reported. Foam height is readimmediately after the solution settled (t=0). Three replicates are donefor each sample, and the reported foam height (in mL) is the averagereading of the three replicates.

Ross Miles foam height data for compound of Example 3 are recorded inTable 2. The foam height trend obtained from the Ross Files foam heighttest agreed with the simple shake foam tests used in this work,indicating that example 3 is a surfactant that provides stable foam.

TABLE 2 Product of Ross Miles foam Dynamic surface Contact angle onExample No. (mm) tension (dynes/cm) Teflon (°) 3 0 min: 150 71 (4bubbles/s) 70 5 min: 135

Example 9 Water Solubility

Selected N-alkyl pyroglutamic acids are converted into their sodium saltby neutralizing them in water with sodium hydroxide. In general, a knownamount of sample is placed in a vial and a known amount of water isadded. Sample is neutralized with 25 wt % sodium hydroxide in wateruntil pH is >7. Mild heating (50° C.) is applied when necessary to aiddissolution. The final mass is recorded. The weight percent of thesolution is determined by mass of the sodium salt over the total mass ofsolution, and multiplying by 100. The pH of the solution is recordedafter neutralization. The water solubility results are summarized inTable 3. No effort was done to prepare a saturated solution. All theexamples tested for water solubility (example 1, 2, 4, 6) in Table 4have high water good water solubility (>10 wt %).

TABLE 3 Product of Example No. Solubility (wt %) pH 1 24.3 10.0 2 21.47.3 4 15.4 7.1 6 26.9 7.0

It is understood that the examples and embodiments described herein arefor illustrative purposes only. Unless clearly excluded by the context,all embodiments disclosed for one aspect of the invention can becombined with embodiments disclosed for other aspects of the invention,in any suitable combination. It will be apparent to those skilled in theart that various modifications and variations can be made to the presentinvention without departing from the scope of the invention. Thus, it isintended that the present invention cover the modifications andvariations of this invention provided they come within the scope of theappended claims and their equivalents. All publications, patents, andpatent applications cited herein are hereby incorporated herein byreference for all purposes.

1. A compound of the formula (I):

or acceptable salts, hydrates, or solvates thereof; wherein R₁ ishydrogen, C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, M⁺, or a polyoxyalkylenemoiety having oxyalkyl groups that are the same or different, and wherethe polyoxyalkylene moiety is capped or uncapped; where M⁺ is a cationforming a salt; R₂ and R₃ are independently C₂-C₂₄ alkyl, C₂-C₂₄alkenyl, or C₂-C₂₄ alkynyl, each optionally substituted with one or moreof R₄; and wherein R₄ is halogen, —CN, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆alkynyl, C₁-C₆ haloalkyl, —NH(C₁-C₆ alkyl), —N(C₁-C₆ alkyl)₂, —OH, C₁-C₆alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl),—CON(C₁-C₆ alkyl)₂, C₃-C₈ cycoalkyl, aryl, heteroaryl, or heterocyclyl,wherein each cycloalkyl, aryl, heteroaryl, and heterocyclyl areoptionally substituted with one or more of halogen, —CN, C₁-C₆ alkyl,C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆ alkyl), —N(C₁-C₆ alkyl)₂, —OH, C₁-C₆alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl),or —CON(C₁-C₆ alkyl)₂; or R₄ is polyoxyalkylene moiety having oxyalkylgroups that are the same or different, and where the polyoxyalkylenemoiety is capped or uncapped.
 2. A compound according to claim 1,wherein R₁ is hydrogen or M⁺.
 3. A compound according to claim 1,wherein R₁ is a polyoxyalkylene moiety having oxyalkyl groups that arethe same or different, and where the polyoxyalkylene moiety is capped oruncapped.
 4. A compound according to claim 1, wherein R₂ is C_(n) alkyl,and R₃ is C_(n-2) alkyl, each optionally substituted with one or more ofR₄, and wherein n is 4-12.
 5. A compound according to claim 4, wherein nis 5 or
 10. 6. A compound according to claim 1, which is:


7. A composition comprising a compound according to claim 1, and atleast one additive, excipient or diluent.
 8. A composition comprising atleast two compounds selected from the compounds of formula (II):

or acceptable salts, hydrates, or solvates thereof; wherein R₅ ishydrogen, C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, M⁺, or a polyoxyalkylenemoiety having oxyalkyl groups that are the same or different, and wherethe polyoxyalkylene moiety is capped or uncapped; where M⁺ is a cationforming a salt; R₆ is unbranched or branched C₂-C₂₄ alkyl, unbranched orbranched C₂-C₂₄ alkenyl, unbranched or branched C₂-C₂₄ alkynyl, C₃-C₈cycloalkyl, or C₃-C₈ cycloalkyl(C₁-C₆ alkyl), each optionallysubstituted with one or more of R₇, and wherein R₇ is halogen, —CN,C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆ alkyl), —N(C₁-C₆ alkyl)₂,—OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆ alkyl),—CON(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl)₂, C₃-C₈ cycloalkyl, aryl,heteroaryl, or heterocyclyl, wherein each cycloalkyl, aryl, heteroaryl,and heterocyclyl are optionally substituted with one or more of halogen,—CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆ alkyl), —N(C₁-C₆alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆ alkyl),—CON(C₁-C₆ alkyl), or —CON(C₁-C₆ alkyl)₂, and of formula (III):

or acceptable salts, hydrates, or solvates thereof; wherein each R₈ isindependently hydrogen, C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, M⁺, or apolyoxyalkylene moiety having oxyalkyl groups that are the same ordifferent, and where the polyoxyalkylene moiety is capped or uncapped;where M⁺ is a cation forming a salt; R₉ is unbranched or branched C₂-C₂₄alkyl, unbranched or branched C₂-C₂₄ alkenyl, unbranched or branchedC₂-C₂₄ alkynyl, O₃—C₈ cycloalkyl, or C₃-C₈ cycloalkyl(C₁-C₆ alkyl), eachoptionally substituted with one or more of R₁₀; and wherein R₁₀ ishalogen, —CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆ alkyl),—N(C₁-C₆ alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆alkyl), —CON(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl)₂, C₃-C₈ cycloalkyl, aryl,heteroaryl, or heterocyclyl, wherein each cycloalkyl, aryl, heteroaryl,and heterocyclyl are optionally substituted with one or more of halogen,—CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆ alkyl), —N(C₁-C₆alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆ alkyl),—CON(C₁-C₆ alkyl), or —CON(C₁-C₆ alkyl)₂.
 9. A composition according toclaim 8 further comprising at least one additive, excipient or diluent.10. A composition according to claim 8, comprising at least twocompounds of formula (II).
 11. A composition according to claim 10,comprising at least two compounds that are:


12. A composition according to claim 12, comprising at least twocompounds that are:


13. A compound according to claim 1, for use as a surfactant, surfaceactive additive, or phase transfer catalyst.
 14. A compound according toclaim 1 for use in personal care formulations.
 15. A method of preparinga compound of formula (IV) or a mixture of one or more compounds offormula (IV):

or acceptable salts, hydrates, or solvates thereof; wherein R₁₁ ishydrogen, C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, M⁺, or a polyoxyalkylenemoiety having oxyalkyl groups that are the same or different, and can becapped or uncapped; where M⁺ is a cation forming a salt; R₁₂ isunbranched or branched C₃-C₂₄ alkyl, unbranched or branched C₃-C₂₄alkenyl, or unbranched or branched C₃-C₂₄ alkynyl, each optionallysubstituted with one or more of R₁₅; and wherein R₁₅ is halogen, —CN,C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆ alkyl), —N(C₁-C₆ alkyl)₂,—OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆ alkyl),—CON(C₁-C₆ alkyl), —CON(C₁-C₆ alkyl)₂, C₃-C₈ cycloalkyl, aryl,heteroaryl, or heterocyclyl, wherein each cycloalkyl, aryl, heteroaryl,and heterocyclyl are optionally substituted with one or more of halogen,—CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, —NH₂, —NH(C₁-C₆ alkyl), —N(C₁-C₆alkyl)₂, —OH, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, —CO₂H, —CO₂(C₁-C₆ alkyl),—CON(C₁-C₆ alkyl), or —CON(C₁-C₆ alkyl)₂; comprising treating aglutamate of formula:

wherein each R₁₄ is independently selected form hydrogen, M⁺, C₁-C₆alkyl, C₁-C₆ hydroxyalkyl, —(C₁-C₆ alkyl-0)₁₋₄H, aryl, aryl(C₁-C₆alkyl), or polyoxyalkylene unit; with an aldehyde of formula:

wherein R₁₃ is C₁-C₂₃ alkyl, C₂-C₂₃ alkenyl, or C₂-C₂₃ alkynyl, eachoptionally substituted with one or more of R₁₅.
 16. A personal careformulation comprising a compound according to claim
 1. 17. A personalcare formulation comprising a composition according to claim
 7. 18. Amethod for carrying out phase transfer in a reaction system comprisingadding to the system a compound according to claim
 1. 19. A method forcarrying out phase transfer in a reaction system comprising adding tothe system a composition according to claim
 7. 20. A personal careformulation according to claim 16, where the formulation is a shampoo ora body wash formulation.